Faculty Collaboration Database

A novel alpha 2-adrenoceptor antagonist attenuates the early, but preserves the late cardiovascular effects of intravenous dexmedetomidine in conscious dogs. J Cardiothorac Vasc Anesth 1998 Aug;12(4):429-34

Date

08/26/1998

Pubmed ID

9713732

DOI

10.1016/s1053-0770(98)90197-5

Scopus ID

2-s2.0-0031830347 (requires institutional sign-in at Scopus site)   50 Citations

Abstract

OBJECTIVES: To test the hypothesis that L-659,066, a peripherally acting alpha 2-adrenoceptor agonist, will abolish the early pressor response but preserve the late depressor action of intravenous dexmedetomidine in conscious, unsedated dogs.

DESIGN: A prospective investigation.

SETTING: A laboratory research.

PARTICIPANTS: Nine chronically instrumented dogs.

INTERVENTIONS: Dogs received dexmedetomidine, 5 micrograms/kg intravenously, in the presence or absence of L-659,066, 0.1, 0.2, or 0.4 mg/kg intravenously, pretreatment in a random fashion determined with a Latin square design on different experimental days.

MEASUREMENTS AND MAIN RESULTS: Systemic and coronary hemodynamics were assessed under control conditions, 30 minutes after administration of L-659,066 and 5 and 60 minutes after intravenous administration of dexmedetomidine. Dexmedetomidine alone acutely increased mean arterial pressure (106 +/- 3 to 175 +/- 4 mmHg; p < 0.05), left ventricular (LV) systolic and end-diastolic pressures, systemic vascular resistance (3,400 +/- 350 to 13,360 +/- 2,290 dyne.s.cm-5; p < 0.05), and coronary vascular resistance (2.69 +/- 0.19 to 4.18 +/- 0.43 mmHg.Hz-1.10(-2); p < 0.05) and decreased LV +dP/dtmax and cardiac output (2.6 +/- 0.3 to 1.3 +/- 0.2 L/min; p < 0.05). Dexmedetomidine alone decreased heart rate, mean arterial pressure, and LV systolic pressure and caused sustained reductions in +dP/dtmax and cardiac output up to 60 minutes after administration. L-659,066 alone increased heart rate, +dP/dtmax, cardiac output, and coronary blood flow velocity and decreased systemic vascular resistance. Mean arterial and LV pressures and coronary vascular resistance were unchanged. Pretreatment with L-659,066 abolished the acute dexmedetomidine-induced increases in mean arterial pressure, LV pressures, systemic and coronary vascular resistance and decreases in +dP/dtmax and cardiac output. In contrast, reductions in mean arterial pressure and LV systolic pressure observed 60 minutes after administration of dexmedetomidine were preserved in dogs receiving L-659,066. Cardiac performance, systemic vascular resistance, and coronary hemodynamics were also maintained to a greater degree 60 minutes after dexmedetomidine administration in the presence of L-659,066.

CONCLUSION: L-659,066 prevents the immediate pressor effects of 5 micrograms/kg of intravenous dexmedetomidine but preserves the majority of the late beneficial cardiovascular effects of this selective alpha 2-adrenoceptor agonist in conscious dogs.

Author List

Pagel PS, Proctor LT, Devcic A, Hettrick DA, Kersten JR, Tessmer JP, Farber NE, Schmeling WT, Warltier DC

MESH terms used to index this publication - Major topics in bold

Adrenergic alpha-Agonists
Adrenergic alpha-Antagonists
Animals
Blood Flow Velocity
Blood Pressure
Cardiac Output
Consciousness
Coronary Circulation
Coronary Vessels
Dogs
Drug Interactions
Heart Rate
Hemodynamics
Hypnotics and Sedatives
Imidazoles
Injections, Intravenous
Medetomidine
Prospective Studies
Quinolizines
Random Allocation
Time Factors
Vascular Resistance
Vasoconstrictor Agents
Ventricular Function, Left
Ventricular Pressure